Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000619108 | SCV000735518 | uncertain significance | Cardiovascular phenotype | 2018-09-24 | criteria provided, single submitter | clinical testing | The p.R1150L variant (also known as c.3449G>T), located in coding exon 22 of the TRPM4 gene, results from a G to T substitution at nucleotide position 3449. The arginine at codon 1150 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002491310 | SCV002789743 | uncertain significance | Progressive familial heart block type IB; Erythrokeratodermia variabilis et progressiva 6 | 2021-08-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002531740 | SCV003450209 | uncertain significance | Progressive familial heart block type IB | 2021-12-24 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 518560). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1150 of the TRPM4 protein (p.Arg1150Leu). |